Repetitive use of levosimendan in advanced heart failure: need for stronger evidence in a field in dire need of a useful therapy

Pölzl, Gerhard; Altenberger, Johann; Baholli, Loant; Beltrán, Paola; Borbély, Attila; Comín‐Colet, Josep; Delgado, Juan; Fedele, Francesco; Fontana, Antonella; Fruhwald, Friedrich; Giamouzis, Grigorios; Giannakoulas, George; García-González, Martín J.; Gustafsson, Finn; Kaikkonen, Kari; Kivikko, Matti; Kubica, Jacek; Lewinski, Dirk von; Löfman, Ida; Malfatto, Gabriella; Manito, Nicolás; Martínez-Sellés, M.; Masip, Josep; Merkely, Béla; Morandi, Fabrizio; Mølgaard, Henning; Oliva, Fabrizio; Pantev, Emil; Papp, Zoltán; Perna, Gian Piero; Pfister, Roman; Piazza, V Di; Bover, Ramón; Rangel‐Sousa, Diego; Recio-Mayoral, Alejandro; Reinecke, Alexander; Rieth, Andreas; Sarapohja, Toni; Schmidt, Günter; Seidel, Mirko; Störk, Stefan; Vrtovec, Bojan; Wikström, Gerhard; Yerly, Patrik; Pollesello, Piero

doi:10.1016/j.ijcard.2017.05.081

Cited by 31 publications

(34 citation statements)

References 49 publications

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“…5 Recently, sacubitril/valsartan, 8 ivabradine, 9 and cardiac resynchronization therapy 10 were found to reduce both hospitalizations and rehospitalizations. 18,19 In this paper, the design of the randomized, double-blind, placebo-controlled LeoDOR (levosimendan infusions for patients with advanced chronic heart failure) trial is presented. 12 Levosimendan, a calcium sensitizer and potassium channel opener, is indicated for acute HF.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, a larger study is needed to verify these favourable preliminary results. 18,19 In this paper, the design of the randomized, double-blind, placebo-controlled LeoDOR (levosimendan infusions for patients with advanced chronic heart failure) trial is presented. This study will assess the efficacy and safety of intermittent levosimendan therapy started during the vulnerable phase following a hospitalization for acute HF.…”

Section: Introductionmentioning

confidence: 99%

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Repetitive levosimendan infusions for patients with advanced chronic heart failure in the vulnerable post‐discharge period

et al. 2018

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Hospitalization for acute heart failure (HF) is associated with a substantial morbidity burden and with associated healthcare costs and an increased mortality risk. However, few if any major medical innovations have been witnessed in this area in recent times. Levosimendan is a first‐in‐class calcium sensitizer and potassium channel opener indicated for the management of acute HF. Experience in several clinical studies has indicated that administration of intravenous levosimendan in intermittent cycles may reduce hospitalization and mortality rates in patients with advanced HF; however, none of those trials were designed or powered to give conclusive insights into that possibility. This paper describes the rationale and protocol of LeoDOR (levosimendan infusions for patients with advanced chronic heart failure), a randomized, double‐blind, placebo‐controlled, international, multicentre trial that will explore the efficacy and safety of intermittent levosimendan therapy, in addition to optimized standard therapy, in patients following hospitalization for acute HF. Salient features of LeoDOR include the use of two treatment regimens, in order to evaluate the effects of different schedules and doses of levosimendan during a 12 week treatment phase, and the use of a global rank primary endpoint, in which all patients are ranked across three hierarchical groups ranging from time to death or urgent heart transplantation or implantation of a ventricular assist device to time to rehospitalization and, lastly, time‐averaged proportional change in N‐terminal pro‐brain natriuretic peptide. Secondary endpoints include changes in HF symptoms and functional status at 14 weeks.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Repetitive levosimendan infusions for patients with advanced chronic heart failure in the vulnerable post‐discharge period

et al. 2018

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“…Levosimendan also acts via activation of ATP-sensitive K + channels (Grossini et al 2009). In clinical trials levosimendan exhibited non-consistent results, especially in terms of mortality (Mebazaa et al 2007; Polzl et al 2017; Landoni et al 2017). …”

Section: Troponin Tropomyosin and Ca2+: How Force Is Producedmentioning

confidence: 99%

New Insights in Cardiac Calcium Handling and Excitation-Contraction Coupling

Gambardella

Trimarco

Iaccarino

et al. 2017

Advances in Experimental Medicine and Biology

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Excitation-contraction (EC) coupling denotes the conversion of electric stimulus in mechanic output in contractile cells. Several studies have demonstrated that calcium (Ca2+) plays a pivotal role in this process. Here we present a comprehensive and updated description of the main systems involved in cardiac Ca2+ handling that ensure a functional EC coupling and their pathological alterations, mainly related to heart failure.

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“…Patients with AdvHF are inherently unstable and begin to decompensate well before being hospitalized [2,57]. As illustrated in Fig.…”

Section: Inotropes In Advanced Heart Failurementioning

confidence: 99%

A pragmatic approach to the use of inotropes for the management of acute and advanced heart failure: An expert panel consensus

Farmakis

Agostoni

Baholli

et al. 2019

International Journal of Cardiology

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Inotropes aim at increasing cardiac output by enhancing cardiac contractility. They constitute the third pharmacological pillar in the treatment of patients with decompensated heart failure, the other two being diuretics and vasodilators. Three classes of parenterally administered inotropes are currently indicated for decompensated heart failure, (i) the beta adrenergic agonists, including dopamine and dobutamine and also the catecholamines epinephrine and norepinephrine, (ii) the phosphodiesterase III inhibitor milrinone and (iii) the calcium sensitizer levosimendan. These three families of drugs share some pharmacologic traits, but differ profoundly in many of their pleiotropic effects. Identifying the patients in need of inotropic support and selecting the proper inotrope in each case remain challenging. The present consensus, derived by a panel meeting of experts from 21 countries, aims at addressing this very issue in the setting of both acute and advanced heart failure.

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Repetitive use of levosimendan in advanced heart failure: need for stronger evidence in a field in dire need of a useful therapy

Cited by 31 publications

References 49 publications

Repetitive levosimendan infusions for patients with advanced chronic heart failure in the vulnerable post‐discharge period

Repetitive levosimendan infusions for patients with advanced chronic heart failure in the vulnerable post‐discharge period

New Insights in Cardiac Calcium Handling and Excitation-Contraction Coupling

A pragmatic approach to the use of inotropes for the management of acute and advanced heart failure: An expert panel consensus

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